{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:43:48Z","timestamp":1791395028736,"version":"4.3.3"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The rodent <jats:italic>Pig\u2010a<\/jats:italic> assay is a flow cytometric, phenotype\u2010based method used to measure in vivo somatic cell mutation. An Organization for Economic Co\u2010operation and Development (OECD) test guideline is currently being developed to support routine use of the assay for regulatory purposes (OECD project number 4.93). This article provides advice on best practices for designing and conducting rodent <jats:italic>Pig\u2010a<\/jats:italic> studies in support of evaluating test substance safety, with a focus on the rat model. Various aspects of assay conduct, including laboratory proficiency, minimum number of animals per dose group, preferred treatment and blood sampling schedule, and statistical analysis are described.<\/jats:p>","DOI":"10.1002\/em.22427","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T08:46:28Z","timestamp":1613810788000},"page":"227-237","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Recommendations for conducting the rodent erythrocyte <i>Pig\u2010a<\/i> assay: A report from the <scp>HESI GTTC<\/scp><i>Pig\u2010a<\/i> Workgroup"],"prefix":"10.1002","volume":"62","author":[{"given":"Stephen D.","family":"Dertinger","sequence":"first","affiliation":[{"name":"Litron Laboratories  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed A.","family":"Bhalli","sequence":"additional","affiliation":[{"name":"Covance Laboratories Inc.  Greenfield Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Charles River Laboratories  Skokie Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Leon F.","family":"Stankowski","sequence":"additional","affiliation":[{"name":"Charles River Laboratories  Skokie Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Bhaskar","family":"Gollapudi","sequence":"additional","affiliation":[{"name":"Toxicology Consulting  Midland Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Lovell","sequence":"additional","affiliation":[{"name":"St. George's University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Recio","sequence":"additional","affiliation":[{"name":"Integrated Laboratory Systems  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Kimoto","sequence":"additional","affiliation":[{"name":"Teijin Pharma Limited  Hino Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daishiro","family":"Miura","sequence":"additional","affiliation":[{"name":"Teijin Pharma Limited  Hino Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Heflich","sequence":"additional","affiliation":[{"name":"U.S. Food and Drug Administration\/NCTR  Jefferson Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22249"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9646-9_2"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/026119290303101s06"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41021-019-0121-z"},{"key":"e_1_2_12_6_1","article-title":"Standard protocol for the PIGRET assay, a high\u2010throughput reticulocyte Pig\u2010a assay with an immunomagnetic separation, used in the interlaboratory trial organized by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen and Genome Society","author":"Chikura S.","year":"2021","journal-title":"Genes and Environment"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.2307\/1267913"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2020.503256"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22312"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2011.01.009"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20671"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0223-2_18"},{"key":"e_1_2_12_13_1","unstructured":"EFSA (European Food Safety Authority). (2017)Scientific Opinion (DRAFT for public consultation): reflection on interpretation of some aspects related to genotoxicity assessment. Available at:https:\/\/www.efsa.europa.eu\/sites\/default\/files\/engage\/170724.pdf."},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2014.09.007"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-018-0016-5"},{"key":"e_1_2_12_16_1","unstructured":"ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use). (2017)M7(R1): assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk. Available at:https:\/\/www.ema.europa.eu\/en\/ich-m7-assessment-control-dna-reactive-mutagenic-impurities-pharmaceuticals-limit-potential. [Accessed 4th November 2020]."},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geu051"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20677"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2011.03.016"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geu055"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.4248\/BR201303001"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22320"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600781r"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7680492"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/00224065.1984.11978921"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22145"},{"key":"e_1_2_12_27_1","unstructured":"NIH (National Institutes of Health). (2015)Consideration of sex as a biological variable in NIH\u2010funded research. Available at:https:\/\/grants.nih.gov\/grants\/guide\/notice-files\/NOT-OD-15-102.html."},{"key":"e_1_2_12_28_1","unstructured":"OECD (Organisation for Economic Cooperation and Development). (2016)Overview of the set of OECD Genetic Toxicology Test Guidelines and updates performed in 2014\u20102015. ENV Publications. Series on Testing and Assessment No. 234 OECD Paris. Available at:http:\/\/www.oecd.org\/officialdocuments\/publicdisplaydocumentpdf\/?cote=ENV-JM-MONO(2016)33\/rev1&doclanguage=en."},{"key":"e_1_2_12_29_1","unstructured":"OECD (Organisation for Economic Cooperation and Development). (2020a)Thein vivoerythrocytePig\u2010agene mutation assay \u2010 Part 1: detailed review paper and performance analysis (Publication 315). Available at:http:\/\/www.oecd.org\/chemicalsafety\/testing\/series-testing-assessment-publications-number.htm."},{"key":"e_1_2_12_30_1","unstructured":"OECD (Organisation for Economic Cooperation and Development). (2020b)Thein vivoerythrocytePig\u2010agene mutation assay\u2014Part 2: validation report (Publication 316). Available at:http:\/\/www.oecd.org\/chemicalsafety\/testing\/series-testing-assessment-publications-number.htm."},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfp289"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22060"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22402"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2019.503106"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22211"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21981"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.20687"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.22298"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.2307\/2685212"}],"container-title":["Environmental and Molecular Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/em.22427","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/em.22427","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/em.22427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T11:47:11Z","timestamp":1693568831000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/em.22427"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/em.22427"],"URL":"https:\/\/doi.org\/10.1002\/em.22427","archive":["Portico"],"relation":{},"ISSN":["0893-6692","1098-2280"],"issn-type":[{"value":"0893-6692","type":"print"},{"value":"1098-2280","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"2021-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}